The present invention relates to a method of crystalline lens replacement. More particularly, the present invention relates to a method of crystalline lens replacement for restoring optical properties, such as clarity and refraction, of the lens suffering from defects (e.g., cloudiness, complete opacification or loss of transparency) due to cataracts or other diseases, while keeping the ability of the normal lens to accommodate resulting from the relaxation and contraction of the ciliary muscle.
Cataract is a disease involving partial or complete opacity in/on the lens or capsule of the eye(s), which could result in significant loss of eyesight or even blindness. Cataracts can be classified to congenital or acquired, and known acquired cataracts include senile (age-related), diabetic and traumatic cataracts as well as other types thereof that may develop upon exposure to energy such as ultraviolet or nuclear radiation. Among these, senile cataracts are one of the most commonly found disorders of the middle aged and elderly persons, of which patients have increased through recent improvements in living conditions, nutrition, and medical infrastructures resulting in an increase in life expectancy.
Several procedures are used in the therapeutic treatment of cataracts. One technique is called extracapsular lens extraction that involves surgical removal of the cloudy lens cells, leaving the outer membrane lens capsule intact. Once the content of the lens is removed, cataract glasses, contact lenses or intraocular lenses may be utilized for replacement so that the post-extraction corrective eyesight is provided. The term xe2x80x9cintraocular lensxe2x80x9d as used herein means a plastic lens having an optic (lens body) and haptics (fixation elements), in which the optic is made of a molded polymer or a hydrated polymer gel and each haptic comes out of the optic to adjoin the lens to the iris or capsule. Intraocular lenses (IOLs) are artificial lenses that have been rapidly widespread because they can provide with better eyesight than glasses or contact lenses after surgery, the posterior capsule can be left in its place by virtue of the established procedures such as ultrasonic phacoemulsification, and good post-surgical results have afforded at a lower rate of complications. The intraocular lenses may be made of a hard plastic material such as polymethylmethacrylate (PMMA), or of either a soft hydrated polymer such as poly(2-hydroxyethylmethacrylate) and poly(N-vinyl-2-pyrrolidone) or a soft non-hydrated material such as silicon rubber and acrylic rubber.
The crystalline lens of the normal eyes usually accommodate by changing their shapes to allow the eyes to adjust their focal point. On the other hand, the above-mentioned plastic intraocular lenses having a predetermined shape are disadvantageous owing to their inabilities of adjusting their focal point. In this respect, intraocular lenses with multifocal optics are also employed to adjust for both short- and long-range eyesight. However, such multifocal IOLs rely on the pupil that serves as the aperture stop in an optical system, so that they provide with double images, namely simultaneously distant and near images, which may result in unpleasant visual experiences. In particular, the elderly persons can hardly accommodate themselves to such new experiences in eyesight, therefore clinical applications of the multifocal IOLs have been significantly limited. In addition, the above-described surgical procedure also has a problem involved in a relatively large hole required for removal of the lens substance and placement of the intraocular lens.
Taking into account of such circumstances, implantation of a soft artificial lens that can change its form has been attempted to provide accomodation of a natural lens. For example, J. Kessler reported that refilling of the lens capsule with clear injectable silicone compounds in animal eyes can restore the shape of a normal lens (Kessler J. Experiments in refilling the lens, Arch. Ophthalmol. 71 [3]:412-417 (1964)). However, time-dependent leakage of the injected liquid silicone deforms the lens in a relatively short period of time, thus resulted in difficulty in keeping appropriate eyesight of the patient. Accordingly, such a refilling procedure cannot be applied in practice to an in vivo treatment of cataracts.
Some other conventional procedures have been developed to overcome the above-mentioned problems, for example: (1) a method comprising injection of an intraocular lens composition containing a photo-polymerizable monomer and a photoinitiator directly into a lens capsule after removal of the lens substance, or into an intracapsular balloon or a capsule of a thin film that was inserted into the lens capsule (Japanese Patent Laid-open No. 2-255151); and (2) a method comprising replacement of the natural lens with a balloon or a capsule of a thin film into which a polymer solution or a cross-linking gel is injected after removal of the lens substance (Japanese Patent Laid-open No. 1-227753).
The above first approach is disadvantageous in: that no accommodation can be achieved due to the formation of a solid intraocular lens in the lens capsule; that only insufficient eyesight can be provided because of difficulties in forming an intraocular lens of an exactly desirable shape; that the monomer and/or photoinitiator may affect harmfully in in vivo upon absorption into the body of organisms; and that sterilization of the composition is rather difficult.
The above second approach of injecting the liquid polymer into the balloon is disadvantageous in that it is difficult to conform the balloon to the shape of the lens capsule even when an elastomer is used as the material of the balloon, and that only insufficient and unstable visual performance can be obtained. Furthermore, since a fairly large incision in the sclera, cornea, and/or lens capsule is required, the procedure is much invasive for the patient.
Accordingly, an object of the present invention is to provide a method of ophthalmic treatment of diseases such as cataracts with a good prognosis by means of replacing the lens suffering from defects (e.g., cloudiness, complete opacification or loss of transparency) due to cataracts or other diseases, while keeping the functions (e.g., accommodative ability) and the fundamental structure of the normal lens to restore optical properties, such as clarity and refraction, with minimal invasive operation to the lens and its circumferential tissues.
The present inventors have established the following method comprising the steps of:
(1) forming a small hole penetrating through a crystalline lens capsule for removing crystalline lens cells that are clouded and opacified, and for refilling an injectable composition directly into the lens capsule thereafter, so that the hole may be as small as possible with a smooth periphery;
(2) removing the opacified crystalline lens substance without damaging the hole;
(3) refilling directly into the lens capsule an injectable composition that is safe for an organism, capable of being readily injected without any damage to the hole, to yield suitable refractive power; and
(4) firmly closing the hole after the injectable composition is directly refilled into the lens capsule.
A first aspect of the present invention is to provide a method of crystalline lens replacement, comprising the steps of:
(1) forming a small hole penetrating through a crystalline lens capsule;
(2) removing at least a part of the crystalline lens substance through the hole;
(3) refilling the crystalline lens capsule with an injectable composition to be refilled directly into the lens capsule comprising a hydrophilic polymer through the hole; and
(4) closing the hole.
In this first aspect of the present invention, it is preferable that the hole may be closed by using a hole closure comprising a rod-shaped member made of a gel or a soft plastic material having an enlarged portion provided at the tip of the rod-shaped member, a marginal protruding piece provided at a middle part of the rod-shaped member, and a closed tubular section provided along the axial center of the rod-shaped member.
In the preferred embodiment, the hole closure may have the closed tubular section penetrating from a tip of the enlarged portion to a tail end of the rod-shaped member, alternatively, the closed tubular section may be formed such that it extends from inside the enlarged portion to the tail end of the rod-shaped member while enabling to pass through the length from the anterior edge of the closed tubular section to the tip of the enlarged portion.
Moreover, it is preferable that the hole closure includes a rigid tubular member that is longitudinally slidable in the closed tubular section and removable therefrom.
Furthermore, it is preferable that the step (4) described above may be carried out by: inserting the rigid tubular member in the closed tubular section of the hole closure; inserting the enlarged portion provided on the tip of the closure into the crystalline lens through the hole; pinching a portion of the lens capsule surrounding the hole with a rear edge surface of the enlarged portion and an anterior edge surface of the marginal protruding piece; and then pulling out the rigid tubular member, thereby closing the hole with the remaining closure.
A second aspect of the present invention is to provide to a method of crystalline lens replacement, comprising the steps of:
(1) forming a small hole penetrating through a crystalline lens capsule;
(2) inserting a rigid tubular member that is longitudinally slidable in and removable from a closed tubular section, into the closed tubular section of a hole closure comprising a rod-shaped member made of a gel or a soft plastic material having an enlarged portion provided at the tip of the rod-shaped member, a marginal protruding piece provided at a middle part of the rod-shaped member and the closed tubular section provided along the axial center of the rod-shaped member, thereafter inserting said enlarged portion through the hole into the crystalline lens;
(3) ejecting a head of the rigid tubular member from the tip of the enlarged portion, and removing the crystalline lens substance through the rigid tubular member;
(4) refilling the crystalline lens capsule with an injectable composition to be refilled directly into the lens capsule comprising a hydrophilic polymer through the rigid tubular member; and
(5) pinching a portion of the lens capsule surrounding the hole with a rear edge surface of the enlarged portion and an anterior edge surface of the marginal protruding piece, and then pulling out the rigid tubular member thereby closing the hole with the remaining closure.
Preferably, the hole closure for use in the first and second aspects of the present invention may have a separate removable ring member as the marginal protruding piece, and the rigid tubular member that is longitudinally slidable in and removable from the closed tubular section. In addition, the gel may preferably comprise cross-linked polyvinyl alcohol, and the soft plastic may be preferably silicon rubber.
In the present invention described heretofore, it is preferable that 1 to 90% by weight of hydrophilic polymer may be contained in the injectable composition to be refilled directly into the lens capsule.
Furthermore, it is preferable that the injectable composition to be refilled directly into the lens capsule may have a viscosity of 50,000 cP or lower, an index of refraction of 1.340 or higher and a visible light transmittance of 50% or more. Moreover, in the preferred embodiment of the invention, the hydrophilic polymer may be at least one polymer selected from the group consisting of polyvinyl alcohol polymers, polyvinyl pyrrolidone polymers and polyethylene glycol polymers, and more preferably, the hydrophilic polymer may comprise a polyvinyl alcohol polymer and a polyvinyl pyrrolidone polymer. When such an injectable composition is directly refilled into the lens capsule followed by closing, a shape can be achieved substantially corresponding to the natural shape of the crystalline lens before removing the lens substance, and thus, an accommodative ability can be imparted to the lens implant on the basis of the changes in the shape of the crystalline lens resulting from the relaxation and contraction of the ciliary muscle, as is originally found in a natural crystalline lens.
In the preferred embodiment of the above-mentioned present invention, the subject of the method of replacement may be animals including human, particularly a patient suffering from cataract, wherein the opacified crystalline lens substance may be removed at the step (2).
In yet further embodiment of the present invention, the hole may be preferably formed by irradiation of laser beam, or by using a cystotome hand piece at the step (1). In the case in which the hole is formed by irradiation of the laser beam, a light guide may be preferably used which comprises a condensing lens having a focal length of 1 to 500 mm provided on a tip of the guide. Meanwhile, it is preferable that the cystotome hand piece may comprise a rotary shaft, a first motor for rotating the rotary shaft, a second motor for longitudinally moving the first motor and the rotary shaft integrally, a trepan bar removably attached to a tip of the rotary shaft, a fixed outer casing through which the trepan bar is inserted, and negative pressure application means for applying a negative pressure to an interspace of an inside of the trepan bar and/or between the trepan bar and the fixed outer casing, wherein the rotary shaft provided integrally with the first motor is moved forward through the second motor to eject a tip of the trepan bar from the outer casing during the hole forming operation, and the rotary shaft provided integrally with the first motor is usually moved backward through the second motor to store the tip of the trepan bar within the outer casing.
A preferred embodiment of the present invention is described below in more detail.